Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14,14-Octamethyl-1,4,8,11-Tetraazacyclotetradecanes

Three isomeric Me8[14]anes, LA, LB and LC, undergo complexation with copper(II) salts to form a series of [CuLXn(H2O)x]Xy.(H2O)z complexes where L = LA, LB and LC; X = Cl, Br, NO3; n, x, y and z may have values of 0, 1 or 2. The complexes have been characterised on the basis of analytical, spectroscopic, magnetic and conductance data. Further, the X-ray crystal structure of one complex, [CuLB(OH2)2](NO3)2, has been determined. The antifungal activity of all three isomeric ligands and their complexes has been investigated against a range of phytopathogenic fungi.


Introduction
The importance of synthetic macrocycle complexes is well recognised and hardly needs elaboration. This contribution focuses on the synthesis and characterisation of a series of copper(ll) complexes of isomeric octamethyl tetraazatetradecanes. It has been shown that 1,2propanediamine condenses with acetone stereospecifically to yield only the 3,10-C-meso isomer of the macrocycle 3,5,7,7,10,12,14,14-octamethyl-1,4,8,1 1-tetraazacyclotetradeca-4,1 1-diene, Me8114]diene, L1; this assignment is based on 1H NMR [1, 2] and has been confirmed by X-ray crystallography [3]. "%'* N N H H N N L1 The reduction of L1 with NaBH4 yields three isomeric Me8114]anes, i.e. LA, LB and Lc, as revealed by a 1H NMR study and, in the case of LB, by an X-ray crystallographic study [4]. The interactions of these ligands with certain metal centers have been investigated previously.
In one study [5], a number of square planar copper(ll) complexes were prepared by the reaction, in methanolic solution, of copper perchlorate with LA, LB and Lc; in each case two diastereoisomers were isolated. Owing to the steric hindrance of the eight methyl groups in these macrocycles and the non-coordinating tendency of perchlorate, it was expected that the preparation of five-or sixcoordinate complexes may be difficult [5]. Subsequently, in another study,  reported the preparation of a series of six coordinate cobal.t(lll) complexes with these isomeric ligands, i.e. [CoLCI2](CIO4); N-chiral isomers have been separated. Hence, it seemed likely that Volume 4, No. 5, 1997 Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14, 14-Octamethyl-1, 4, 8,11-Tetraazacyclotetradecanes higher coordination number copper(ll) salts could also be prepared. In this context, a number of new fourand six-coordinate copper(ll) complexes have been isolated and their antifungal activities, as well as those of the ligands, investigated. [CuLc(NO3)(H20)]NO3--Lc (0.312 g, 1.0 mmol) and Cu(NO3)2.3H20 (0.241 g, 1.0 mmol) were dissolved in dry EtOH (40 ml). The resulting blue mixture was heated on a steam bath for ca 30 min and then filtered. The purple filtrate was concentrated on a steam bath for a further 25 min until the volume was reduced to 10 ml. After cooling to room temperature, the blue product, [CuLc(NO3)(H20)]NO3, was filtered off, washed with iprOH and Et20.  , 9.14; N, 11.62 %. C18H44CuCI2N402 requires C, 44.72; H, 9.12; N, 11.61%. After separating the violet product, the violet mother liquor was concentrated to ca 5 ml. On cooling, a brown product precipitated. After 45 min, the product, [CuLB]CI2.2H20, was filtered off and washed with dry EtOH, followed by Et20 and dried in vacuo; m. pt > 280 C. Found C,44.73;H,9.11;N,11.63 %. C18H44CuCI2N402 requires C, 44.72; H, 9.12; N, 11.61%.
The brown product turns violet when heated in an oven at 70C for ca 5 min. On exposure to air the violet product reverts back to brown.
[CuLc]CI2 and [CuLcCI2].2H20--Lc (0.312 g, 1.0 mmol) and CuCI2.2H20 (0. [CuLcBr2].2H20 Lc (0.312 g, 1.0 mmol) and CuBr2 (0.223 g, 1.0 mmol) were dissolved separately in hot absolute EtOH (15 ml) and mixed. A blue-violet color appeared immediately. The mixture was evaporated to dryness on a steam bath The crude, dried product was extracted with chloroform. Some red product remained undissolved but there was insufficient for characterisation. The chloroform extract was taken to dryness on a steam bath to yield a blue

Antifungalactivities
The antifungal activity of the isomeric ligands and their copper complexes (in vitro) against some selected phytopathogenic fungi was assessed by the poisoned food technique. Potato Dextrose Agar (PDA) was used as a growth medium. DMF was used as solvent, initially to prepare solutions of the compounds. The solutions were then mixed with the sterilised PDA to maintain the concentration of the compounds at 0.01%; 20 ml of these were each poured into a petri dish.
After the medium had solidified, a 5 mm myceial disc for each fungus was placed in the centre of each assay plate against the control. Linear growth of the fungus was measured in mm after five days of incubation at 25 + 2C.

Results and discussion
On the basis of their 1H and 3C NMR spectra [4], LA, LB and Lc have been assigned structures as shown in the Introduction; and the structure of LB confirmed by X-ray crystallography [4]. On reaction with copper(ll) salts, the isomeric ligands yield both four-and six-coordinate complexes of the general formula: [CuLXn(H20)x]Xy.(H20)z, where L LA, LB and Lc; X CI, Br, NO3; n, x, y and z may have values of 0, or 2. As 1H NMR could not be measured for these paramagnetic salts, exact stereochemistries could not be determined except for that of [CuLB(H20)2](NO3)2 for which a single crystal structure analysis could be undertaken. Characterisation of the complexes could be achieved using IR and UV/vis spectroscopies as well as by magnetochemical and conductance measurements. Physical and spectroscopic data are collected in Tables and 2. In principle [6, 10], owing to the presence of four chiral N-centers in LA, LB and Lc, each isomer Me8114]ane can yield 16 diastereoisomeric complexes of the same geometry. Out of these possibilities, only a few are stable and sufficiently abundant to permit their isolation in the solid state. In this study, only one diastereoisomer of each complex was isolated.
The IR spectrum of [CuLA(NO3)2].H20 exhibits a band at 1380 cm"1, similar to that found in the spectrum of the free ligand [11], which can be assigned to absorptions due to CH3 groups. Two bands, at 1435 cm -1 and 1325 cm -, are attributed to coordinated NO3 groups. The separation of 110 cm " between the two bands indicates a unidentate mode of coordination. Moreover, a band at 250 cm "1 can be assigned to M-O stretching of a unidentate NO 3 group [12]. The presence of lattice water is indicated by the presence of bands at 3440 cm " and 1626 cm"1. Selected IR bands for all complexes are collected in Table 1. The conductance value at 9 ohm -1 cm 2 mol " (see Table  "r" 2) in DMF solution shows that the complex is essentially a non-electrolyte, however, in water a 1:2 electrolyte is indicated as H20 replaces NO 3" in the coordination sphere.
It has been shown that copper(ll) centres in macrocycles generally have square planar or tetragonally distorted octahedral geometries and that these give rise to broad bands in the visible region due to overlap of Alg Big, B2g Big and Eg--Big transitions [13]. The [CuLA(NO3)2].H20 complex shows a broad d-dband at 558 nm in DMF and 516 nm in water (Table  2) consistent with the above. The magnetic moment is 1.80 BM (Table 2), i.e. consistent with the copper(ll) complex having one unpaired electron.
The IR spectrum of [CuLB(H20)2](NO3) 2 exhibits an intense, sharp band at 1380 cm "1 which is attributed to ionic, non-coordinating NO3 and methyl groups. A sharp VOH band at 3430 cmis due to coordinated water and further evidence for this assignment is found in a band at 445 cm -1 which is attributed to M-O stretching. The conductance in water shows a 1:2 electrolyte, however, in DMF, where the colour changes to pink-violet, the conductance value is indicative of an 1:1 electrolyte. This result is accounted for by NO3 coordinating the copper center in DMF solution as has been seen in similar systems [14]. The magnetic moment and electronic data are consistent with an octahedral structure. Unambiguous structure determination has been afforded by a crystallographic analysis.

14-Octamethyl-1, 4, 8,11-Tetraazacyclotetradecanes
The copper(ll) cation is located on a crystallographic center of inversion and exists in a tetragonally distorted octahedral geometr)/defined by a N402 donor set. The Cu-N(1) and Cu-N(4) separations of 2.039(2) A and 2.029(2) A, respectively are equal to each other and the independent Cu-O(1) separation is 2.853(2) A. The four N-chiral centers of 14-membered ring are in the 1RS, 4RS, 8SR 11 SR configuration with two NH groups above the N 4 equatorial plane and the other two below. The methyl groups of the five-membered rings occupy axial positions and those in the sixmembered rings, i.e. bound to C(5), occupy equatorial positions. The geometry reported here i'esembles cloosely that found in [CuLB(H20)2](CIO4)2 where the Cu-N distances were 2.035 (3) and 2.031 (4) A, and Cu-O is 2.815(5) A; the configuration of the four N-chiral centers was 1SR, 4RS, 8SR, 11SR with a similar disposition of the N_H groups [15]. Trans configurations as shown in Fig. have   during the course of the synthesis. A blue solution yielded this product and this suggested that a different diastereoisomer or geometric isomer was abundant in solution but only the brick-red product was stable in the solid state.
The IR spectrum of [CuLACI2].H20 displays vOH and 5OH bands corresponding to lattice water. A band at 275 cm -1 is assigned to Cu-CI stretching. The molar conductivity in DMF (6 ohm "1 cm 2 mol1) shows that the complex is a non-electrolyte. Based on the above evidence, a distorted octahedral geometry is proposed for [CuLACI2].H20.
The interaction of LB with copper(ll) chloride gives brown [CuLB]CI2.2H20 and violet [CuLBCI2].2H20. The brown product is obtained at room temperature and the violet product can be isolated in the absence of water or by heating the brown product to 70 80C. Moreover, the violet complex reverts to the brown one on exposure to moisture.
The IR spectrum of brown [CuLB]CI2.2H20 reveals a sharp vOH and 5OH bands indicating lattice water; the absence of any M-O band around 450 cm "1 confirms that water is not coordinated in this complex. Further, n,o bands are seen around 250 cm 1 indicating that the chloride is not coordinating. The electronic spectrum was not well resolved.
The IR spectrum of violet [CuLBCI2].2H20 shows a similar pattern to that found for [CuLB]CI2.2H20 except for the appearance of an additional band at 240 cm -1 which is assigned to a M-CI stretching frequency. The non-electrolytic nature of this complex in DMF solution strongly supports a tetragonally distorted octahedral complex.
An almost violet colour is observed when the brown complex is dissolved in DMF solution and the conductance (14 ohm "1 cm 2 mo1-1) corresponds to a non-electrolyte. This (Table 2)indicate normal behaviour for these d 9 systems. This study demonstrates that it is possible to form tetragonally distorted octahedral copper(ll) complexes with the sterically congested LA, LB and Lc isomeric macrocycles with eight peripheral methyl groups, in particular with smaller anions. Thus, complexes with LA, having four equatorial methyl groups, allowed axial coordination of all anions investigated in this study. The diaxial-diequatorial arrangement of the methyl substituents in LB precluded coordination of nitrate. By contract, Lc, having three equatorial methyl groups allowed the coordination of one nitrate anion only. Volume 4, No. 5, 1997 Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14, 14-Octamethyl-1,4, 8,11-Tetraazacyclotetradecanes 3.5 Fungitoxicity study The antifungal activities of the isomeric macrocycles and some of their complexes are summarised in  Screens have been conducted against three selective phytopathogenic fungi: i) Alternaria altemata, ii) Curvalaria lunata, and iii) Macrophomina phaseolina. The activities of the three ligands and their complexes against Altemaria altemata are greater than those against the other two fungi. The activities of the three macrocycles were similar and were found to decrease upon coordination to copper(ll).
The fungitoxicities are generally lower that those of related sulfur-containing Schiff bases and their complexes [18], however, it is noteworthy that the decrease in activity upon coordination of the respective ligands is less in the present study.